# HCC Risk Stratification in MAFLD Cirrhosis

> **NIH NIH P01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $763,507

## Abstract

The etiological risk factors for hepatocellular carcinoma (HCC) and its precursor lesion (cirrhosis) in the US have
dramatically changed in the past decade from predominantly active chronic viral hepatitis (hepatitis B and C) to
Metabolic (dysfunction) Associated Fatty Liver Disease (MAFLD). Given the high prevalence of the
metabolic disorders (e.g., obesity and diabetes) that define MAFLD and their chronic incurable nature, the focus
on HCC prevention related to MAFLD is paramount. Prevention of HCC requires better understanding of the
determinants of this risk, and the consequent construction of models and tools for risk stratification. We propose
to leverage data, biospecimens and infrastructure of the Texas HCC Consortium (THCCC) Cohort, the largest
US-based active prospective cohort study of cirrhosis patients, of whom 80% is estimated to have MAFLD. We
propose expanding and extending the follow-up of the THCCC cohort to >5000 patients with >350 incident HCC
cases. Our study in Project 1 has the following Specific Aims:
1. Identify metabolic risk factors for HCC in a large contemporary prospective cohort of patients with
cirrhosis. We will examine associations of existing and novel metabolic candidate markers including (1) MAFLD
phenotypic features: body mass index, waist-to-hip ratio, triglyceride level, HDL cholesterol level, diabetes, and
markers of insulin resistance, (2) select novel metabolic biomarker candidates identified using metabolomic and
lipidomic assays of samples from a discovery case-control study nested within THCCC, and (3) suspected
molecular markers of metabolic dysfunction (e.g., serum adipokines level, pro/anti-inflammatory cytokines).
2. Identify demographic, lifestyle features, genetic risk factors, and liver imaging markers associated
with the risk of developing HCC among patients with cirrhosis. We will examine associations of the risk of
HCC with candidate risk factors/markers i.e., (1) demographic (age, race/ethnicity, sex) and lifestyle (smoking,
physical activity) features, (2) a polygenic risk score based on established genetic markers of MAFLD (PNPLA3,
TM6SF3, MBOAT7, NCAN, PP1R3B), and (3) novel quantitative imaging markers of body fat (skin-to-liver-
capsule distance) and liver fat (hepatorenal index) estimated from radiomic analyses of liver ultrasound images.
3. Develop and optimize adaptive risk indices for predicting risk of progression to HCC among patients
with cirrhosis. We will develop a set of adaptive models including (a) a ‘basic’ index that combines demographic
and lifestyle predictors with phenotypic metabolic predictors, (b) add blood-based markers (e.g., a polygenic risk
score, metabolic risk score) to the ‘basic’ index, and (c) add liver ultrasound radiomics indices. We will assess
the performance characteristics of the risk prediction indices
The risk prediction index will have important translational implications to the comparative cost effectiveness of
HCC prevention (e.g., chemopreventio...

## Key facts

- **NIH application ID:** 10874532
- **Project number:** 5P01CA263025-03
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Hashem B El-Serag
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $763,507
- **Award type:** 5
- **Project period:** 2022-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10874532

## Citation

> US National Institutes of Health, RePORTER application 10874532, HCC Risk Stratification in MAFLD Cirrhosis (5P01CA263025-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10874532. Licensed CC0.

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